6j7b: Difference between revisions
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==Crystal structure of VASH1-SVBP in complex with epoY== | |||
<StructureSection load='6j7b' size='340' side='right'caption='[[6j7b]], [[Resolution|resolution]] 1.62Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6j7b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J7B FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.618Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BJL:(2~{S})-2-[[(3~{R})-4-ethoxy-3-oxidanyl-4-oxidanylidene-butanoyl]amino]-3-(4-hydroxyphenyl)propanoic+acid'>BJL</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6j7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j7b OCA], [https://pdbe.org/6j7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j7b RCSB], [https://www.ebi.ac.uk/pdbsum/6j7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j7b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/VASH1_HUMAN VASH1_HUMAN] Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096).<ref>PMID:15467828</ref> <ref>PMID:16488400</ref> <ref>PMID:16707096</ref> <ref>PMID:19204325</ref> <ref>PMID:29146869</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
alpha-Tubulin detyrosination, largely catalyzed by vasohibins, is involved in many microtubule (MT)-related cellular events. In this study, we identified a core heterodimeric complex of human small vasohibin-binding protein (SVBP) and vasohibin 1 (VASH1) (hereafter denoted as SVBP-VASH1) that catalyzes the detyrosination of a peptide derived from C-terminus of alpha-tubulin. We further solved the crystal structures of the SVBP-VASH1 heterodimer alone and in complex with either an inhibitor or a mutant substrate peptide. Our structural research, complemented by biochemical and mutagenesis experiments, resulted in identification of the key residues for VASH1 binding to SVBP and alpha-tubulin substrate. Our in vivo experiments reveal that MT detyrosination in general, as well as the interactions between SVBP, VASH1, and alpha-tubulin, are critical for spindle function and accurate chromosome segregation during mitosis. Furthermore, we found that the phenotypes caused by the depletion of vasohibins were largely rescued upon co-depletion of kinesin13/MCAK, suggesting the coordination between the MT depolymerase and MT detyrosination during mitosis. Thus our work not only provides structural insights into the molecular mechanism of alpha-tubulin detyrosination catalyzed by SVBP-bound vasohibins, but also uncovers the key role of vasohibins-mediated MT detyrosination in spindle morphology and chromosome segregation during mitosis. | |||
Molecular basis of vasohibins-mediated detyrosination and its impact on spindle function and mitosis.,Liao S, Rajendraprasad G, Wang N, Eibes S, Gao J, Yu H, Wu G, Tu X, Huang H, Barisic M, Xu C Cell Res. 2019 Jun 6. pii: 10.1038/s41422-019-0187-y. doi:, 10.1038/s41422-019-0187-y. PMID:31171830<ref>PMID:31171830</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6j7b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bao H]] | |||
[[Category: Huang H]] | |||
[[Category: Wang N]] | |||
[[Category: Wu B]] | |||